162 results about "PHA binding" patented technology

The invention relates to the field of antitumor drugs, in particular to a pharmaceutical composition of a KRAS G12C inhibitor and Ly2090314 and application of the pharmaceutical composition. According to the invention, the Ly2090314 and the KRAS G12C inhibitor are combined to play a synergistic effect, a DNA damage repair pathway is inhibited, a better inhibition effect is generated on tumor cells containing KRAS G12C mutation, the dosage required for achieving the same anti-tumor effect is greatly reduced, and the medication safety is improved.

The invention belongs to the technical field of nano-medicines and targeted therapy, and particularly relates to a targeted nano-system nano-drug delivery system based on mesoporous polydopamine as well as a preparation method and application thereof, in particular to an N2E4-MPDA-Gem nano-system based on mesoporous polydopamine (MPDA). A targeting nano system based on mesoporous polydopamine comprises mesoporous polydopamine nano particles loaded with pancreatic cancer chemotherapy drugs, targeting molecules N2E4 are combined with the surfaces of the mesoporous polydopamine nano particles, and phenylboronic acid coatings used for controlling drug release are arranged on the surfaces of the mesoporous polydopamine nano particles. The system adopts a modular design, can be compatible with various chemotherapeutic drugs such as oxaliplatin, irinotecan and the like, and can be flexibly coupled with different targeting antibodies such as EGFR (epidermal growth factor receptor), HER2 (human epidermal growth factor receptor) and the like. A standard preparation process and good stability provide reliable guarantee for clinical transformation, and the compound shows an excellent treatment effect in a solid tumor model represented by pancreatic cancer.

The present invention relates to anti-CD37antibodies having an Fc-Fc interaction enhancing substitution in the Fc-region of a human IgG, for use as a medicament in combination with anti-CD20 antibodies having an Fc-Fc interaction enhancing substitution in the Fc-region of a human IgG. The invention also relates to a novel composition of anti-CD37 antibodies having an Fc-Fc 5 interaction enhancing substitution and anti-CD20 antibodies having an Fc-Fc interaction enhancing substitution. In particular, the invention relates to compositions wherein the anti-CD37 antibody binds human CD37 and the anti-CD20 antibody binds human CD20. The invention also relates to compositions where the composition is a pharmaceutical composition and the use of such compositions in treatment of cancer and other diseases.

The invention relates to the technical field of organelle separation, and provides a combination of ATF6 alpha N protein and peroxisome, application of the ATF6 alpha N protein in separation and purification of the peroxisome and a method for separating and purifying the peroxisome. The ATF6 alpha N protein is combined with membrane protein PMP70 and / or ABCD1 of the peroxisome; the method comprises the following steps: combining tagne-ATF6 alpha N fusion protein with a medium to obtain a fusion protein-medium compound; adding a roughly separated peroxisome sample into the fusion protein-medium compound, so as to obtain a fusion protein-medium-peroxisome compound; and adding an elution buffer solution, and collecting the eluent to obtain the peroxisome combined with the fusion protein. The method is easy and convenient to operate, complex instruments and equipment are not needed, the peroxisome can be separated from cells and tissues, and the obtained peroxisome is high in purity and can be used for conventional experiments such as subsequent protein spectrum analysis and flow analysis.

Provided herein are methods of separating molecular species of a guanine-rich oligonucleotide from a mixture of molecular species, wherein at least one molecular species of the mixture is a quadruplex formed from the guanine-rich oligonucleotide. In exemplary embodiments, the methods comprise (a) applying the mixture to a chromatographic matrix comprising a hydrophobic ligand, wherein said hydrophobic ligand comprises C4 to C8 alkyl chains, wherein molecular species bind to the hydrophobic ligand and (b) applying a mobile phase which comprises a gradient of acetate and a gradient of acetonitrile but no cationic ion pairing agent to the chromatographic matrix to elute molecular species of the guanine-rich oligonucleotide. In exemplary aspects, the guamne-rich oligonucleotide elutes in a first set of elution fractions and a quadruplex formed from the guanine-rich oligonucleotide elutes in a second set of elution fractions.

The invention belongs to the technical field of biomedicine, and discloses an antinuclear antibody IgG indirect immunofluorescence detection method and system, and the detection standardization degree and the result reproducibility are significantly improved through the full-automatic system design in combination with precise mechanical transmission and an automatic sample adding device. Through an optimized FITC labeling system and a refined washing procedure, non-specific binding is remarkably reduced, and meanwhile, the binding efficiency of the antinuclear antibody and the secondary antibody is improved, so that the detection sensitivity is improved. Through the design of the automatic sample adding and sheet sealing device, the sample treatment efficiency is greatly improved, and simultaneous detection of large-scale samples can be realized. Through combination of a high-resolution imaging system and an intelligent image analysis algorithm, morphological characteristics and distribution rules of fluorescence signals are automatically extracted, and the accuracy and objectivity of a detection result are greatly improved.

The invention discloses an application of CLASP2 protein in preparation of a medicine for promoting spinal cord injury repair. According to the invention, a bioinformatics and phosphorylated proteomics technology combined method is utilized to screen out that the functional protein of curcumin for promoting spinal cord injury repair is CLASP2 protein. The molecular biological technique verifies that curcumin regulates and controls microtubule stability by increasing phosphorylation of CLASP2 protein to promote functional repair after spinal cord transection injury. Therefore, the curcumin can regulate and control microtubules by promoting the phosphorylation of the CLASP2 to dynamically promote the motor function repair after the spinal cord injury of the mouse. The method has an important application value.

The invention relates to the technical field of biological detection, and discloses a method for double-ring detection of lung cancer L858R mutation based on CRISPR / Cas9 and DNA, and the method comprises the following steps: enriching circulating tumor cells CTC from a blood sample; extracting genomic DNA (deoxyribonucleic acid) of the enriched CTC; carrying out amplification on the DNA fragment containing the L858R mutation by adopting recombinase polymerase amplification RPA (recombinase polymerase amplification); the amplified DNA fragment is hybridized with a recognition ring in a DNA double-ring structure, a DNA double ring is composed of the recognition ring and a report ring, and a part of region of the recognition ring is hybridized with a corresponding fragment of the report ring to form a staggered double-chain region; when L858R mutation exists, the mutated DNA and a recognition ring are hybridized to activate a CRISPR / Cas9 system, and under the guidance of sgRNA, Cas9 cuts hybrid double strands and releases a report ring; carrying out rolling circle amplification RCA under the action of DNA polymerase by taking the released report ring as a template; a fluorescent probe is used for detecting an RCA amplification product, and whether L858R mutation exists or not is judged according to a fluorescence signal. The CRISPR / Cas9 system is combined with a DNA double-ring structure, so that the ultra-sensitive and specific detection on the lung cancer L858R mutation is realized.

The present application relates to an anti-CD3 antibody and its application. The present application develops a specific antibody molecule targeting CD3 epsilon chain, which can activate T cells by combining with CD3 epsilon on T cells. A T cell binding protein containing the CD3 antibody is further designed, which can specifically target and bind to CD3 epsilon on the surface of T cells in vivo and in vitro, so as to achieve moderate activation of T cells. The CAR lentivirus containing the T cell binding protein of the present application can induce the generation of CAR-T cells in vitro and in vivo, and the CAR-T cells have good tumor cell killing efficiency.

The invention provides a method and a device for secondary filtration and re-removal of cholesterol ester after continuous blood purification and blood fat filtration, and belongs to the technical field of medical blood purification. According to the method and the device, the technology of combining enzymolysis, adsorption and membrane separation is adopted for residual CE in a CBP filtering product. The method comprises the following steps: firstly, decomposing CE into small molecules by using specific enzyme, and weakening the combination of CE and other components; residual impurities are further adsorbed through a high-performance adsorption material; and finally, efficient removal of CE is realized by virtue of a high-precision membrane separation technology, so that the residual quantity is reduced to be below a safety threshold value. Compared with a traditional technology, the problems that the CE-containing filtrate is high in recycling risk and low in resource utilization rate are effectively solved, the purity of a filtered product is remarkably improved, technical support is provided for industrial scenes such as plasma exchange, filtrate feedback, biopharmacy and extracorporeal circulation in the medical field, and the application prospect is wide. The safety and the resource utilization efficiency of the blood purification technology are promoted.

The invention relates to a method for splitting, assembling and site-specific integration of large-fragment exogenous DNA (deoxyribonucleic acid) in Trichoderma reesei. Comprising the following steps: (1) constructing an arg:: Ptcu-Cas9-TtrpC-hph strain containing a Cas9 protein; (2) constructing a pUC19 <-> integration site: a pyr4 plasmid; (3) obtaining a plurality of target gene segments containing integration site homologous arms and having overlapping regions at the tail ends of adjacent DNA segments; (4) obtaining a gRNA expression cassette of a targeted genome integration site; (5) arg conversion: the arg is converted into a Ptcu-Cas9-TtrpC-hph strain; and (6) screening and verifying. According to the method, the CRISPR / Cas9 system is combined with the TAR in the trichoderma reesei for the first time, the exogenous large-fragment DNA is split into a plurality of small fragments, then the plurality of small-fragment exogenous DNA are assembled in the trichoderma reesei and are subjected to fixed-point integration, one-step editing of the large-fragment exogenous DNA is realized, and compared with a traditional genetics method, the gene editing efficiency in the trichoderma reesei is greatly improved.

The invention discloses a one-step biosensor, and aims to solve the problems that a traditional detection device is tedious in steps and needs multiple operations to complete the detection process. The device mainly comprises a substrate layer and a channel layer, liquid with same or different specific biomolecules flows through multiple groups of gold particles through multiple groups of specific pipelines, so that the specific biomolecules are hung on the gold particles, whole blood in the channel layer is separated into plasma and blood cells through electrodes on the substrate layer, and after the plasma and a buffer solution are fully mixed, the blood cells in the channel layer are separated. The method comprises the following steps: enabling the plasma to flow through gold particles decorated by specific biomolecules, and combining target molecules in the plasma with the specific biomolecules to realize red shift and color change of SPR peaks, so that the same or different target molecules are identified, and the content of the target molecules is judged.

The present invention relates to a GPC3xCD3 bispecific antibody, a GPC3xCD28 bispecific antibody, and a combination of two agonistic fully human κλ antibodies, one targeting GPC3xCD3 and the other targeting GPC3xCD28, both of which do not compete for binding to GPC3. The present invention also relates to the use of the bispecific antibodies for the treatment of GPC3-positive malignancies.

The present invention relates to a construct comprising a cell-penetrating peptide sequence coupled by a peptide bond to at least one first linker molecule which is coupled by a peptide bond to the N-terminal end of an interfering amino acid sequence selected from the following sequences: SEQ ID NO:1 which forms the 2104-2206 domain of the human FlnA protein and SEQ ID NO:2 which defines the 330-350 domain of the UT receptor, the sequences having at least 90% identity and, preferably, at least 95% identity with the aforementioned sequences and sequences substantially homologous to the aforementioned sequences and preferably derived from the latter by one or more conservative substitutions.

It is provided an anti-Aβ34 antibody and its use for diagnosing Alzheimer's disease in a patient, comprising obtaining a sample from the patient, detecting the level of Aβ34 in the sample by contacting the sample with the anti-Aβ34 antibody and detecting binding between Aβ34 and the antibody, and diagnosing the patient with Alzheimer's disease when the presence of Aβ34 in the sample is detected, alone or in combination with detecting an amyloid deposition marker such as Aβ42 and determining the ratio of Aβ34 / Aβ42.

The present application relates to the technical field of RNA extraction, and particularly relates to a pretreatment reagent, a method and a kit for RNA purification of whole blood samples. By introducing hydrophobic DESs as the core pretreatment component, the DESs are mixed with the whole blood sample in advance, the DESs form an independent phase layer after centrifugation by using the unique physicochemical properties, and the liposoluble drug components, inflammatory proteins and pigments are selectively extracted to the hydrophobic DESs phase and the RNA is preliminarily purified; the upper water phase of the pretreatment and purification is taken and added into a lysis solution containing a chaotropic salt to fully release the nucleic acid, and DNase I is introduced for digestion. The present application combines the pretreatment of hydrophobic DESs and the digestion of DNase I, and is used in combination with PVP (targeting adsorption of residual pigments and phenolic compounds), reduces the impurities of the lysis system through the front-end pretreatment, creates a low-interference and high-efficiency purification environment for the specific binding of RNA by the magnetic beads, and forms a synergistic removal network for the interference of complex samples.

The invention discloses an application of Siglec-10 / G or a fusion protein containing a Siglec-10 / G protein structure in preparation of a medicine for treating glioma. The application finds that Siglec-10 / G is a new key myeloid immune checkpoint molecule in a glioma immunosuppression microenvironment, and reveals a specific molecular mechanism that Siglec-10 / G and related action signals (such as MUC1, CKB and GOT1) thereof influence glioma generation. The Rebinant Mouse Siglec-10 (C-Fc) provided by the invention can be combined with a ligand on the surface of a tumor cell, so that endogenous Siglec-10 / G signal transduction on MDM is competitively blocked, the anti-tumor immunity of a tumor-bearing mouse is improved, the growth of glioma is inhibited, the survival time of the tumor-bearing mouse is prolonged, and the Rebinant Mouse Siglec-10 (C-Fc) can be used for treating glioma.

The application belongs to the technical field of biotechnology, and discloses a nano antibody targeting B cell BCMA and application thereof. The amino acid sequences of the complementarity determining regions CDR1-CDR3 of the nano antibody are selected from SEQ ID NO. 1-12. The nano antibody provided by the application can specifically bind to B cells in human blood, especially activated plasma cells, so as to eliminate B cells producing pathological antibodies. Compared with traditional antibodies, the nano antibody provided by the application has a smaller molecular weight, high stability, low cost, easy expression and high expression amount, and is suitable for large-scale production. The nano antibody is combined with a solid-phase carrier in the application, so that B cells in blood can be targeted and eliminated, the number of B cells in blood of patients can be reduced in a short time, and the antibody level can be reduced, thereby improving the quality of life, reducing complications, and providing a new treatment option for patients who are ineffective or intolerant to traditional treatment.

The invention belongs to the technical field of phosphatidylserine production, and particularly relates to immobilized phospholipase D based on biological imprinting and a preparation method and application thereof. The preparation method comprises the following steps: S1, dissolving L-serine in an acetic acid buffer solution to obtain a serine solution, adding a phospholipase D solution into the serine solution, and stirring to obtain a mixed solution; s2, adding sodium alginate into the mixed solution, stirring and dissolving to obtain a biopolymer solution; s3, adjusting the pH value of the chitosan solution to be neutral, then adding CaCl2 into the chitosan solution, and stirring and dissolving to obtain a CaCl2-containing chitosan solution; and S4, dropwise adding the biopolymer solution into a chitosan solution containing CaCl2, complexing to form microspheres, collecting the microspheres, and washing and drying the microspheres to obtain the immobilized phospholipase D based on biological imprinting. According to the method, the biological imprinting technology and the enzyme immobilization technology are combined, the immobilized PLD with high selectivity and high stability is prepared, and the phosphatidyl transfer reaction efficiency is improved.

The present application relates to a kind of sgRNA targeting Plagl1 gene DMR, epigenetic editing system and its application.Specifically, the present application provides sgRNA targeting Plagl1 gene differential methylation region, which forms epigenetic editing system with dCas9-Tet1-CD fusion protein.The system is loaded in injectable type light-cured silk fibroin hydrogel, the expression of Plagl1 gene in periosteum stem / progenitor cells is accurately activated by targeted demethylation modification, thereby promoting osteogenic differentiation.The present application combines epigenetic regulation with biomaterial delivery, and provides a safe, efficient new strategy for jaw bone defect regeneration and repair.

The invention discloses a solid-phase and liquid-phase combined synthesis method of tilpotide, and belongs to the field of chemical synthesis of polypeptide drugs. The method comprises the following steps: firstly, synthesizing a complete main peptide chain of the tiall peptide on a solid phase carrier, and protecting a side chain of lysine (Lys24) at the 24th site by adopting an orthogonal protecting group (Dde), so that side chain activated ester (Ecosanoic acid-gamma-Glu-AEA-AEA-OSu) can be specifically connected to an amino group of lysine (Lys20) at the 20th site, and the protecting group of the Lys24 can be selectively removed under a mild liquid phase condition to obtain crude peptide of the tiall peptide. Complex side chain modification is transferred from a solid phase to a liquid phase, the problems of steric hindrance and low connection efficiency are effectively solved, and the method has the advantages of being high in synthesis purity, few in side reaction, easy to amplify and the like and is suitable for industrial production.

The invention belongs to the technical field of biological medicines, and relates to a mutants of mu-conotoxin KIIIA rich in positive charges and application of the mutants. The mutant is obtained by implementing site-specific mutagenesis at the following positions on a mutant as shown in SEQ ID NO.1 in a sequence table: S6R; the amino acid sequence of the mutant is as shown in SEQ ID NO. 2 in a sequence table. According to the invention, systematic structural optimization is carried out on a parent peptide KIIIA containing three pairs of disulfide bonds, and a strategy of combining disulfide bond deletion and amino acid site-directed mutagenesis is adopted, so that a mutant which is simple and convenient to synthesize and has a remarkable inhibition effect on a NaV1.4 channel is obtained. The mutant has high activity, high stability and better pharmacokinetic characteristics, and has wide development potential.

Exemplary systems, methods, and computer-accessible medium are provided for Chimeric Antigen Receptor (CAR)-T therapy. Thus, the exemplary systems, methods, and computer-accessible medium are provided that select a first set of targets highly expressed in cancer and lowly in normal tissues, select a second set of targets that are highly co-expressed in the cancer and lowly in normal tissues, generate an input set by combining the first and second set of targets with dependency data, single-cell heterogeneity, and antibody availability, determine, by a learning model, at least one target pair for use in CAR-T therapy, and apply a cell therapy based on the determined target pair(s).

The present invention discloses a preparation method and application of a self-assembling polypeptide targeting CD36 protein, belonging to the technical field of biomedicine. The self-assembling polypeptide is composed of an R3 specific targeting unit, an R2 self-assembling unit, and an R1 hydrophobic unit sequentially connected by amide bonds. The R1 hydrophobic unit is an alkyl carboxylic acid with C8-C20, the R2 self-assembling unit is a multiple hydrogen bond polypeptide sequence, and the R3 specific targeting unit is a polypeptide with specific targeting to CD36 protein screened from a polypeptide library. The self-assembling polypeptide of the present invention can bind to CD36. The self-assembling polypeptide of the present invention is obtained by solid-phase synthesis method, and has many advantages such as small relative molecular weight, high specificity, and low cost. It shows unique advantages in the targeted diagnosis and treatment of tumors, and has extremely important and extensive application prospects and good economic and social effects.

The invention discloses a functional small molecule peptide based on eggshell membrane peptide and application of the functional small molecule peptide in drug delivery, and belongs to the field of biological medicine. The invention relates to a functional small molecule peptide based on eggshell membrane peptide, which has pH responsiveness, can target liver cancer, can be prepared into a drug-loaded self-assembly body, and has a structural formula shown in Figure 1. The invention designs a novel small molecule peptide, develops a novel combined treatment scheme of a COX-2 inhibitor and a chemotherapeutic drug, and combines the anti-proliferation effect of DOX and the pro-apoptosis effect of CXB, so as to improve the therapeutic effect of the CXB. The activity of COX2 and the activation of hepatic stellate cells are inhibited, and the synergistic effect of resisting liver cancer is realized. Especially, the pH responsiveness of the experimental peptide Pep is utilized, morphology transformation occurs in a subacid environment, drug excretion and liver cancer proliferation are inhibited, and the functional small molecule peptide capable of enhancing the effect and reducing the toxicity provides a new treatment choice for liver cancer patients.

This invention belongs to the field of biomedical technology, specifically relating to a peptide targeting TRPV1 and its applications. A peptide targeting TRPV1 has the amino acid sequence shown in SEQ ID NO.1. The peptide also includes a mutant obtained by amino acid scanning mutation based on the sequence shown in SEQ ID NO.1. The amino acid sequence of the mutant is shown in any one of SEQ ID NO.2-16. This peptide is used to prepare formulations that block or inhibit TRPV1 activity. This invention provides a peptide targeting TRPV1 and its applications. Through a strategy combining artificial intelligence screening and structural prediction, SEQ ID NO.1 was successfully identified and its mechanism of action was elucidated. Experimental results show that SEQ ID NO.1 and its mutants exhibit excellent analgesic activity and good safety both in vitro and in vivo, demonstrating significant clinical application potential.

The application discloses a TYK2 inhibitor and a screening method and application thereof based on fusion of deep learning scoring and traditional molecular docking scoring. The application adopts a method of combining a deep learning scoring result CNNscore with an empirical scoring result obtained by Watvina, and improves the screening efficiency by multiplying the deep learning docking scoring and the empirical docking scoring, thereby relieving the problem of excessively high false positive rate of the traditional screening method, and saving time and cost. The application also applies the method to 12 million compounds, and verifies the compounds by in-vitro activity test, and obtains two small molecules with TYK2 inhibitory activity, which have application prospects in preventing or / and treating TYK2-mediated diseases. Therefore, the method is helpful to quickly identifying potential effective compounds from a huge compound library.

The invention belongs to the technical field of biological medicines, and relates to a mutants of mu-conotoxin KIIIA rich in positive charges and application of the mutants. The mutant is obtained by carrying out site-directed mutagenesis on C1A, K7R and C15R on a natural mu-conotoxin KIIIA sequence; the amino acid sequence of the mutant is shown as SEQ ID NO. 1 in a sequence table. According to the invention, a series of mutants which are simple and convenient to synthesize and have a remarkable inhibition effect on a NaV1.4 channel are obtained by performing systematic structural optimization on a parent peptide KIIIA containing three pairs of disulfide bonds and adopting a strategy of combining disulfide bond deletion and amino acid site-directed mutagenesis. Furthermore, non-natural amino acid Pen is introduced into the mutant with the optimal activity, so that the stability of the mutant in vivo is remarkably enhanced, and the action time is prolonged.